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Protective vaccination and blood-stage malaria modify DNA methylation of gene promoters in the liver of Balb/c mice

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Abstract

Epigenetic mechanisms such as DNA methylation are increasingly recognized to be critical for vaccination efficacy and outcome of different infectious diseases, but corresponding information is scarcely available for host defense against malaria. In the experimental blood-stage malaria Plasmodium chabaudi, we investigate the possible effects of a blood-stage vaccine on DNA methylation of gene promoters in the liver, known as effector against blood-stage malaria, using DNA methylation microarrays. Naturally susceptible Balb/c mice acquire, by protective vaccination, the potency to survive P. chabaudi malaria and, concomitantly, modifications of constitutive DNA methylation of promoters of numerous genes in the liver; specifically, promoters of 256 genes are hyper(=up)- and 345 genes are hypo(=down)-methylated (p < 0.05). Protective vaccination also leads to changes in promoter DNA methylation upon challenge with P. chabaudi at peak parasitemia on day 8 post infection (p.i.), when 571 and 1013 gene promoters are up- and down-methylated, respectively, in relation to constitutive DNA methylation (p < 0.05). Gene set enrichment analyses reveal that both vaccination and P. chabaudi infections mainly modify promoters of those genes which are most statistically enriched with functions relating to regulation of transcription. Genes with down-methylated promoters encompass those encoding CX3CL1, GP130, and GATA2, known to be involved in monocyte recruitment, IL-6 trans-signaling, and onset of erythropoiesis, respectively. Our data suggest that vaccination may epigenetically improve parts of several effector functions of the liver against blood-stage malaria, as, e.g., recruitment of monocyte/macrophage to the liver accelerated liver regeneration and extramedullary hepatic erythropoiesis, thus leading to self-healing of otherwise lethal P. chabaudi blood-stage malaria.

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Acknowledgements

This project was funded by the National Plan for Science, Technology and Innovation (MAARIFAH), King Abdulaziz City for Science and Technology, Kingdom of Saudi Arabia, awarded number (13-B101206-02).

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Authors and Affiliations

  1. Department of Zoology, College of Science, King Saud University, P.O. Box 2455, Riyadh, 11451, Saudi Arabia

    Saleh Al-Quraishy, Mohamed A. Dkhil & Abdel-Azeem S. Abdel-Baki

  2. Department of Zoology and Entomology, Faculty of Science, Helwan University, Cairo, Egypt

    Mohamed A. Dkhil

  3. Department of Zoology, Faculty of Science, Beni-Suef University, Beni-Suef, Egypt

    Abdel-Azeem S. Abdel-Baki

  4. Epigenetics Core Laboratory, Institute of Transplantation Diagnostics and Cell Therapeutics, Heinrich-Heine-University, Duesseldorf, Germany

    Foued Ghanjati, Lars Erichsen & Simeon Santourlidis

  5. Department of Biology, Heinrich-Heine-University, Duesseldorf, Germany

    Frank Wunderlich

  6. Group of Computational Biology and Systems Biomedicine, Biodonostia Health Research Institute, San Sebastián, Spain

    Marcos J. Araúzo-Bravo

  7. IKERBASQUE, Basque Foundation for Science, Bilbao, Spain

    Marcos J. Araúzo-Bravo

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  1. Saleh Al-Quraishy
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  2. Mohamed A. Dkhil
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  3. Abdel-Azeem S. Abdel-Baki
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  4. Foued Ghanjati
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  6. Simeon Santourlidis
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  7. Frank Wunderlich
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  8. Marcos J. Araúzo-Bravo
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Correspondence to Saleh Al-Quraishy.

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This study was carried out in strict accordance with the German law on animal protection. The keeping of mice and the experimental protocol of the study were officially approved by the State-controlled Committee on the Ethics of Animal Experiments and were regularly controlled, without being previously announced, by the local authorities.

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Al-Quraishy, S., Dkhil, M.A., Abdel-Baki, AA.S. et al. Protective vaccination and blood-stage malaria modify DNA methylation of gene promoters in the liver of Balb/c mice. Parasitol Res 116, 1463–1477 (2017). https://doi.org/10.1007/s00436-017-5423-0

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